Adherence to anti-asthma medications among adult asthmatic patients in Eastern Ethiopia: A multi-center cross-sectional study

Introduction Adherence to anti-asthmatic medications plays a vital role in enhancing an asthma patient’s quality of life and prognosis. However, in Ethiopia, the level of adherence and contributing factors were rarely studied. Therefore, this study was conducted to determine the level of adherence to anti-asthma medications and associated factors among adult asthmatic patients in Eastern Ethiopia. Method Institutional based cross-sectional study was conducted at six governmental hospitals found in Eastern Ethiopia. A total of 320 asthma patients aged 18 years and above and using asthma medicines for at least 12 months were involved. An interviewer based structured questionnaires were used to collect the data. Bivariable and multivariable logistic regression analyses were carried out using IBM SPSS version 22 (SPSS, Chicago, IL). The Adjusted Odds Ratio (AOR) with 95% Confidence Interval (CI) was used to determine the strength of association between independent variables and outcome variable. Variables with a p-value of ≤ 0.05 were considered statistically significant. Result Of the 320 asthma patients that participated in the study, 109(34.1%:28.8–39.1%) of them had good adherence to anti-asthmatic medications. Being a housewife (AOR = 4.265, 95%CI: 1.333, 13.653), having good knowledge about asthma (AOR = 2.921, 95%CI (1.472, 5.795), positive attitude towards asthma (AOR = 3.129, 95%CI: 1.555, 6.293), and use of oral corticosteroid drugs (AOR = 1.967, 95%CI: 1.008, 3.841) were factors positively associated with good adherence to anti-asthmatic medications. Participants on treatment for 2–3 years (AOR = .295, 95%CI: 0.099, 0.873), and those on medication for ≥ 4 years (AOR = 0.229, 95%CI: 0.079, 0.664) were 70.5% and 77.1% times less likely to adhere to anti-asthmatic medications respectively. Conclusion The current study signified a low level of adherence to anti-asthmatic medications. Participant’s characteristics and medication related factors were significantly associated with good adherence to anti-asthmatic medications. Health education and advice during follow-up for asthma patients is crucial for better adherence.


Introduction
Asthma is a chronic condition that inflames and narrows the airways of the lung [1]. According to the World Health Organization (WHO) report, globally, it affected 339 million people in 2018 with the number expected to exceed 400 million by 2025 if the current rising trend continues [2][3][4]. Asthma is an under-diagnosed and undertreated public health problem all over the world [2]. In 2016, 10 out of one million deaths were reported to be due to asthma, with a prevalence of 50% increase per decade and it affects 5%-10% of the total population in low and middle-income countries [5][6][7][8]. Poor-adherence to pharmaceutical treatment is one of the main global challenges in asthma control and treatment [9]. Adherence is the extent to which a patient's behavior corresponds with recommendations from a health care provider [6].
Poor adherence results in increased morbidity, health care utilization, and mortality [9,10]. Williams et al. reported a decrease in the level of adherence by 25%, resulting in a 50% increase in the rate of asthma-related hospitalization [11].
In Ethiopia, adherence to anti-asthmatic medication was reported to be 56.7% in Gondar town [12], and 49.4% in Addis Ababa City [13]. However, according to a recent systematic review and meta-analysis results, nearly 30% of asthmatic patients in Ethiopia have poor adherence to anti-asthmatic medications [14].
Poor adherence to anti-asthmatic medications is determined by factors including lack of education on the proper use of medicines, concerns about the necessity of asthma therapy [9], route of administration, the convenience of the medication administration device, monthly income, comorbidities [13,15,16], adverse drug reaction, and the complexity of the drug regimen [10].
Improving medication adherence in resource-constrained countries like Ethiopia is vital for the effective management of asthma. However, only a few studies elucidate the extent of adherence to anti-asthmatic medications among asthma patients. Furthermore, these studies only focused on a patient's level of adherence to specific types of treatment regimens; inhalation medications [13,15], inadequate sample size and conducted at a single health facility [10,12,17] yielding unrepresentative data. Therefore, the current study was conducted at six different hospitals with adequate sample size, and includes all types of anti-asthmatic medications to assess the level of adherence to anti-asthmatic medications and associated factors among asthmatic patients attending governmental hospitals in Eastern Ethiopia.

Study setting and population
A hospital-based cross-sectional study was conducted from February 21 to April 20, 2020. Study participants were recruited from six government hospitals, namely; Hiwot Fana Comprehensive Specialized Hospital, Jugol General Hospital, and Federal Police Harar General Hospital in Harar region, as well as Dilchora Referral Hospital, Sabian General Hospital, and East Command Level Referral Hospital in Dire Dawa City Administration.
The diagnosis of asthma was based on medical history, physical examination, and spirometer result (based on the Global initiative for asthma diagnosis criteria) [18]. The study population were asthmatic patients who fulfilled the inclusion criteria and were presented at the selected hospitals for follow-up during the data collection period. Inclusion criteria were asthma patients aged 18 years and above and using asthma medicine for at least 12 months. Asthmatic patients who were critically ill and those with severe mental illness, or unable to respond to the questionnaire, as well as those with physician-diagnosed active lung infections, and Chronic Obstructive Pulmonary Disease (COPD) were excluded from the study.

Sample size and sampling procedure
The sample size was calculated using the single population proportion formula [19] by considering the confidence level of 95%, margin of error of 5%, and proportion of adherence to antiasthma medication 33.8% [20]. Accordingly, the final sample size was 343. Participants were recruited from each facility until the allotted number was reached.

Data collection procedures and tools
Data was collected by six nurses with bachelor's degrees under the supervision of a nurse with a master's degree. An interviewer-based structured questionnaire was used.
The questionnaires were first prepared in English, and were translated to the local languages (Amharic, Afaan Oromo, and Af Somali) and translated back to English, whilst ensuring that conceptual equivalence was maintained. The questionnaire included items pertaining to sociodemographic characteristics (sex, marital status, educational status, occupation, residence, and wealth index (a measure of participant's socio-economic status), medication adherence, types of medications used, patient-related factors (having regular follow-up, history of cigarette smoking and chewing khat, attitude towards asthma, knowledge about asthma and family history of asthma), disease-related factors (presence of exacerbation in the past 12 months, comorbidity, and exacerbating factor, history of hospital admission, and duration of treatment).
The Medication Adherence Reporting scale (MARs) that includes ten questions was used to assess the participant's level of drug adherence. The tool was used as it shows good construct, internal, and criterion validity, and was employed by previous locally constructed studies [21,22]. It includes both generic "I use it regularly every day" and asthma-specific questions about medication use "I only use it when I feel breathless"; It also assesses both intentional "I avoid using it if I can", and unintentional non-adherence "I forget to use it" [23]. In order to minimize the social desirability bias, the questions were framed as negative statements. The level of medication use was rated on a five-point Likert scale (1; always to 5; never). Self-reported adherence was reported as the average score of the 10 items (1-5), where higher scores indicate good levels of reported adherence. Good adherence was defined as a MARs score of 4.5 or higher [21,24,25].
The knowledge part of the questionnaire included 20 questions. Participant's scores of at least 50% of each field of knowledge were considered to have good asthma knowledge, and those participants' scores less than 50% were considered to have poor knowledge [26].
The attitude section of the questionnaire included ten questions framed as a positive statement and were scored on a five-point Likert scale ranging from strongly disagree to strongly agree. Accordingly, 1 was given for strongly disagree, 2 for disagree, 3 for neutral, 4 agree, and 5 for strongly agree. Participants with a score � 30 out of 50 were judged to have a positive attitude, while those with a score < 30 were regarded to have a negative attitude [27,28].

Data quality control
Pretest of the questionnaire was conducted on 5% (16) of the sample size at Haramaya Hospital before the actual data collection. Relevant changes were made to the questionnaire after the pretest. Two days of training were given for research assistants and supervisor on the research objectives, data collection tools, procedures, and interview techniques. Data were checked for completeness, consistency, and double data entry done for cross-validation.

Data processing and analysis
Data was checked for completeness and inconsistencies before entering into Epi-data version 3.1.0 and exported to IBM SPSS version 22 (SPSS, Chicago, IL) for analysis. Descriptive statistics including frequencies, proportion, mean, and Standard Deviation (SD) were computed. A wealth index using principal component analysis was carried out to determine participant's socio-economic status. The participant's household wealth was ranked into three quartiles; low, medium, and high. Binary logistic regression analysis was done and all explanatory variables with a p value less than 0.25 on a bivariable logistic regression analysis were entered into a multivariable logistic regression model to identify factors associated with adherence to antiasthma medications [29,30]. The Crude Odds Ratio (COR) and Adjusted Odds Ratio (AOR) along with 95% Confidence Interval (CI) were calculated to measure the strength of association between the independent and outcome variable (level of adherence to anti-asthmatic medications). The fitness of the model was tested by the Hosmer-Lemshow test and was considered fit because it yielded a p value of greater than 0.05 [31,32]. Thus, a p value of less than 0.05 was considered to declare the presence of statistical significance.

Ethical approval
This study was conducted in accordance with the Declaration of Helsinki's ethical principles for medical research involving human subjects. Accordingly, ethical clearance was obtained from Haramaya University, College of Health and Medical Sciences, Institutional Health Research Ethics Review Committee (IHRERC) with reference number (IHRERC/014/2020). An official letter was sent to the selected hospitals for permission to recruit asthma patients. The study participants provided informed, voluntary, and written consent, and they were notified of their right to withdraw their participation in the study at any time. All personal identifiers were excluded; all information obtained was kept confidential, and used for the proposed study only.

Socio-demographic characteristics
A total of 320 individuals participated in the study and a response rate of 93.2% was achieved. The mean age of the participants was 49.9 (±13.39) years, with the range being 18-76 years. Of the total participants, 169(52.8%) were females and 190 (59.4%) were married. One hundred twelve (35%) participants had attended higher education, 160(50%) of them were private employees, and 107 (33.4%) were in the category of high socio-economic status ( Table 1).

Patient-related factors
Of the total study participants, 22(38.1%) attended their regular medical follow-up. The majority of the study participants, 289(90.3%) had never smoked cigarettes and 185(57.8%) of them had the habit of chewing khat. Regarding the knowledge and attitude of the participants towards asthma, 127(39.7%) had poor knowledge about asthma and 165(51.6%) had a positive attitude towards asthma ( Table 2).

Disease related factors
Almost half of the study participants, 155(48.4%), had experienced asthma exacerbation in the past 12 months. Regarding the presence of comorbidity, 130(40.6%) had a comorbid illness and 211(90.2%) participants reported that upper respiratory tract infections precipitated their asthma attack. Only 36(11.3%) of participants reported a history of hospitalization in the previous 12 months, with 17(47.2%) of these admissions attributable to asthma (Table 3).

Factors associated with adherence to anti-asthmatic medications
Factors associated with adherence to anti-asthmatic medications were identified. Age, educational level, occupation, knowledge about asthma, attitude towards asthma, chewing khat,

PLOS ONE
Adherence to anti-asthma medications among adult asthmatic patients.
having regular follow-up, using short-acting beta-agonist drugs, using an oral corticosteroid, presence of comorbidities, presence of precipitating health condition, admission in the previous 12 months, and duration of asthma treatment were all associated with adherence to antiasthmatic medications under bivariable analysis. With further analysis, occupation, knowledge about asthma, attitude towards asthma, using oral corticosteroid drugs, and the duration of asthma treatment were shown to be significantly associated with the outcome variable. Those participants who were housewives were 4.27 times (AOR = 4.27, 95%CI: 1.33, 13.65) more likely to adhere to their anti-asthmatic medications compared to government employees. Furthermore, participants with good asthma knowledge were 2.92 times (AOR = 2.92, 95%CI: 1.47, 5.79) more likely to adhere to anti-asthmatic medications than those with poor asthma knowledge. Similarly, participants with a positive attitude towards asthma were 3.13 times (AOR = 3.13, 95%CI: 1.55, 6.29) more likely to adhere to anti-asthmatic medications than their counterparts with a negative attitude. The odds of good adherence were 1.97 times (AOR = 1.97, 95%CI: 1.00, 3.84) higher for participants on oral corticosteroids than for those on other types of medications. Long-term use of anti-asthmatic medications was associated with a lower level of adherence (Table 4).

Discussion
In this study, the percentage of good adherence to anti-asthmatic medications was 34.1% (CI: 28.8%-39.1%). This is in line with studies conducted in the United States of America and Southern Ethiopia, where the percentage of good adherence to anti-asthma medications were 33.8% and 40.8% respectively [17,20]. However, this finding is higher than the result of a  [12]. However, the current finding is lower than the result of studies conducted in Kenya, 51.5% [33], and in Western Ethiopia, 62.1% [10]. The difference in sample size may contribute to the discrepancy. In our finding, participants identified as housewives were more likely to adhere to antiasthmatic medications than their government employee counterparts. This finding is in contrast to previous results which have shown no significant association between occupation and medication adherence [12,17,34,35]. The finding of the current study could be linked to the fact that housewives could be able to take their medicines on time since they mostly stay at home and visit their doctors regularly, unlike government employees, who may be busy at work. Also, Tomar et al. [36], revealed that under-educated patients were more adherent to anti-asthmatic medications prescribed by health care providers, whereas those who have a better education had a second opinion and decided to alter their treatment. The current study results indicate that participants who had good knowledge of asthma were more likely to have good adherence to anti-asthmatic medications than their counterparts. This finding is in line with previous studies [10,33], which showed that asthmatic patients who had poor knowledge about their disease condition were more likely to be non-adherent to anti-asthmatic medications as compared with those who had good knowledge about asthma.

PLOS ONE
Adherence to anti-asthma medications among adult asthmatic patients.
Patients who had a positive attitude towards asthma were more likely to adhere to the antiasthmatic medications than their counterparts with a negative attitude towards asthma. This finding is supported by the results of a randomized control trial that shows that a positive attitude towards asthma increased the level of medication adherence [37]. In contrast, another study from Southern Ethiopia, shows no significant association between the attitude of asthmatic patients towards asthma and adherence to anti-asthmatic medication [10].
Participants on oral corticosteroid types of medications have better adherence than those on other types of drugs. In contrast, studies conducted in Cameroon and Ethiopia outlined no association between the types of drugs used and the level of adherence to anti-asthmatic medications [38,39]. This discrepancy could be related to the difference in the categories of medications taken by participants, with the current study including seven types of medications while the previously conducted studies included only three categories of anti-asthmatic medications. In the current study, receiving anti-asthmatic medications for a longer period of time was found to be associated with poor medication adherence. According to the study conducted in Cameroon, there was no association between the duration of asthma treatment and adherence to anti-asthmatic medications [38]. This may be related to the fatigue that occurs after taking drugs for an extended period of time [12].

Strengths and limitations
In the current study, standardized, reliable, and validated tools were used to assess patient's level of medication adherence. However, the cross-sectional nature of this study does not show a cause-and-effect relationship between the outcome and independent variables, and the level of medication adherence was assessed by self-report, which may have incurred recall bias. Moreover, the study was not able to illuminate the reason for poor anti-asthmatic medication adherence.

Conclusion and recommendations
This study has demonstrated a low level of adherence to anti-asthmatic medications among participants. Also, we identified personal and medication related factors associated with good adherence to anti-asthmatic medications. Enhancing the level of medication adherence is crucial for the treatment and control of asthma. Health care providers have to counsel and teach asthmatic patients about the benefits of adherence to anti-asthmatic medications. Moreover, we recommend that future researchers to address the limitations of our study through a qualitative approach or mixed-method.